• Luteolin promotes M2 macrophage polarization while suppressing M1 polarization, shifting the inflammatory balance toward tissue repair.
• Luteolin inhibits STING oligomerization and the STING-TBK1 signaling pathway, reducing downstream inflammatory responses.
• In a mouse tibial bone defect model, luteolin alleviates inflammation, enhances angiogenesis, collagen deposition, and bone density.
• Luteolin represents a promising therapeutic agent for bone repair via immunomodulation of macrophage polarization.